Microcirculatory dysfunction during intestinal ischemia-reperfusion

Abstract

Oxido-reductive stress is a crucial factor of the tissue response during ischemia-reoxygenation injuries. Reperfusion affects primarily the microvasculature in a manner consistent with an acute inflammatory reaction. In this respect, the salient data suggest an important connection between endothelial cell-derived humoral mediators and the perivascular mast cell system. Increased endothelin-1 and decreased nitric oxide formation, mast cell degranulation and leukocyte accumulation coexist in gastrointestinal ischemia-reperfusion syndromes too. Constitutively produced nitric oxide inhibits, while increasingly formed endothelin-1 significantly enhances the degranulation of the intestinal mast cells. The endothelin-A receptor-dependent mast cell degranulation per se plays a secondary role in reperfusion-induced structural injury, but contributes significantly to leukocyte recruitment into the reperfused intestinal mucosa. It is conceivable therefore, that the nitric oxide--endothelin-1--mast cell cycle is involved in the mechanism of ischemia-reperfusion-induced endothelial cell-leukocyte interactions, where mast cells act to amplify the process of leukocyte sequestration. The alteration in the balance between endothelial cell-derived proadhesive vasoconstrictor and antiadhesive vasodilator factors exerts a significant influence on the mucosal integrity, and the antagonism of endothelin-A receptor activation in this setting tips the equilibrium toward tissue salvage.

Pretreatment of cromolyn sodium prior to reperfusion attenuates early reperfusion injury after the small intestine ischemia in rats

“…Acute inflammation could lead to increase of IMMC counts and release of a multi-faceted spectrum of proinflammatory mediators by IMMC such as cytokines and chemokines, and MC have the capacity to coordinate trafficking of leukocytes [15] . Boros [16] proved that intestinal ischemia induced the release of a variety of IMMC-derived inflammatory compounds and resulted in a spectrum of injury ranging from reversible permeability changes to structural mucosal damage.…”

Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine

“…Ischemic intestinal disorders including intestinal volvulus, thromboembolic disease, and low flow states associated with shock, have a high mortality rate due to the rapid onset of sepsis and multiple organ failure [1][2][3] . Intestinal ischemic lesions are characterized by sloughing of the apical villus epithelium and rapid breakdown of mucosal barrier function [2,4,5] , accompanied by increased intestinal permeability and subsequent bacterial translocation, sepsis, and multiple organ dysfunction syndrome (MODS) [6][7][8] .…”

Inflammatory Activation after Experimental Cardiac Tamponade

“…Hypoxia is considered to be one of the basic stimuli for ET-1 synthesis. This peptide is produced predominantly by the endothelium, but in pathophysiological states, other cell types such as leukocytes, macrophages, smooth muscle cells, cardiomyocytes and mesangial cells can also serve as sources of its release [12]. The increased plasma level of ET-1 could be responsible for the decreased coronary perfusion [32] and pulmonary hypertension.…”

“…High-mobility group box protein-1 (HMGB1), released passively by necrotic and damaged cells, was recently identified as an important signal for leukocyte recruitment [11]. Further factors identified in the background of PMN leukocyte accumulation are an increased level of endothelin-1 (ET-1) formation and a decreased level of nitric oxide (NO) formation, which coexist in ischemia-reperfusion syndromes [12]. ET-1, one of the most powerful endogenous vasoactive mediators, may contribute to the impairment of the microcirculation through its vasoconstrictor and proadhesive effects [13].…”